1. Field of the Invention
The present invention relates to the delivery of pharmaceuticals and, more particularly, to the use of DNA-capped gold nanoparticles as a delivery mechanism.
2. Description of the Related Art
Metal compounds and complexes are widely used for treating and detecting disease and they are playing an increasingly important role in the emerging field of nanomedicine. Gold nanoparticles (AuNP) in particular offer a number of attractive features for visualization, detection, and treatment of disease. They exhibit a range of surface chemistries for drug or biomaterial modification and, when internalized by the cell, they appear to have minimally toxic effects. For example, DNA-capped AuNP has been used as intracellular gene regulation agents for the control of protein expression in cells, and platinum drugs conjugated to AuNP show considerable promise as chemotherotherapeutic agents. In addition to drug attachment, the NP core itself could be used in treatment strategies and one emerging approach is photothermal therapy, in which the particle is heated to cause damage to the cell.
Most clinically used anticancer drugs have relatively narrow therapeutic windows indicating that the distribution of the drug between normal and diseased tissue is small. For example, the anthracycline antibiotic doxorubicin (DOX, or adriamycin) is a clinically approved chemotherapy agent that binds to DNA via sequence specific intercalation. The binding mechanism involves intercalation of the aglycone portion of the drug at a high affinity site, e.g., 5′-CG/CG, with the daunosamine sugar lying in the minor groove, occluding an additional DNA base pair adjacent to the intercalation site. When bound to DNA, the drug inhibits the enzyme topoisomerase II and the action of DNA polymerase causing cell death. DOX intercalation stabilizes the double-helix, which has been shown to result in an increase in thermal denaturation (e.g. melting) temperature of duplex DNA.